ID   SYFA_HUMAN              Reviewed;         508 AA.
AC   Q9Y285; B4E363; Q9NSD8; Q9Y4W8;
DT   08-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   24-JAN-2024, entry version 214.
DE   RecName: Full=Phenylalanine--tRNA ligase alpha subunit;
DE            EC=6.1.1.20 {ECO:0000269|PubMed:20223217};
DE   AltName: Full=CML33;
DE   AltName: Full=Phenylalanyl-tRNA synthetase alpha subunit;
DE            Short=PheRS;
GN   Name=FARSA; Synonyms=FARS, FARSL, FARSLA;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=9177188; DOI=10.1073/pnas.94.12.6164;
RA   Sen S., Zhou H., Ripmaster T., Hittelman W.N., Schimmel P., White R.A.;
RT   "Expression of a gene encoding a tRNA synthetase-like protein is enhanced
RT   in tumorigenic human myeloid leukemia cells and is cell cycle stage- and
RT   differentiation-dependent.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:6164-6169(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=10049785; DOI=10.1006/bbrc.1999.0141;
RA   Rodova M., Ankilova V., Safro M.G.;
RT   "Human phenylalanyl-tRNA synthetase: cloning, characterization of the
RT   deduced amino acid sequences in terms of the structural domains and
RT   coordinately regulated expression of the alpha and beta subunits in chronic
RT   myeloid leukemia cells.";
RL   Biochem. Biophys. Res. Commun. 255:765-773(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RA   Motegi H., Noda T., Shiba K.;
RL   Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Uterus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Leukocyte, and Lung;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   PROTEIN SEQUENCE OF 2-12.
RC   TISSUE=Platelet;
RX   PubMed=12665801; DOI=10.1038/nbt810;
RA   Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA   Vandekerckhove J.;
RT   "Exploring proteomes and analyzing protein processing by mass spectrometric
RT   identification of sorted N-terminal peptides.";
RL   Nat. Biotechnol. 21:566-569(2003).
RN   [9]
RP   PROTEIN SEQUENCE OF 2-12 AND 326-334, ACETYLATION AT ALA-2, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=B-cell lymphoma;
RA   Bienvenut W.V.;
RL   Submitted (OCT-2004) to UniProtKB.
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-193, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT   kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [11]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [12]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-311, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [13]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [14]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA   Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA   Giglione C.;
RT   "Comparative large-scale characterisation of plant vs. mammal proteins
RT   reveals similar and idiosyncratic N-alpha acetylation features.";
RL   Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN   [15]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-190, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [17]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [18]
RP   INVOLVEMENT IN RILDBC2, AND VARIANTS RILDBC2 LEU-256 AND LYS-410.
RX   PubMed=31355908; DOI=10.1111/cge.13614;
RA   Krenke K., Szczaluba K., Bielecka T., Rydzanicz M., Lange J., Koppolu A.,
RA   Ploski R.;
RT   "FARSA mutations mimic phenylalanyl-tRNA synthetase deficiency caused by
RT   FARSB defects.";
RL   Clin. Genet. 96:468-472(2019).
RN   [19] {ECO:0007744|PDB:3L4G}
RP   X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) IN COMPLEX WITH L-PHENYLALANINE,
RP   CATALYTIC ACTIVITY, AND SUBUNIT.
RX   PubMed=20223217; DOI=10.1016/j.str.2010.01.002;
RA   Finarov I., Moor N., Kessler N., Klipcan L., Safro M.G.;
RT   "Structure of human cytosolic phenylalanyl-tRNA synthetase: evidence for
RT   kingdom-specific design of the active sites and tRNA binding patterns.";
RL   Structure 18:343-353(2010).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-phenylalanine + tRNA(Phe) = AMP + diphosphate + H(+) +
CC         L-phenylalanyl-tRNA(Phe); Xref=Rhea:RHEA:19413, Rhea:RHEA-COMP:9668,
CC         Rhea:RHEA-COMP:9699, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:58095, ChEBI:CHEBI:78442,
CC         ChEBI:CHEBI:78531, ChEBI:CHEBI:456215; EC=6.1.1.20;
CC         Evidence={ECO:0000269|PubMed:20223217};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19414;
CC         Evidence={ECO:0000305|PubMed:20223217};
CC   -!- SUBUNIT: Heterotetramer; dimer of two heterodimers formed by FARSA and
CC       FARSB. {ECO:0000269|PubMed:20223217}.
CC   -!- INTERACTION:
CC       Q9Y285; Q9P2A4: ABI3; NbExp=3; IntAct=EBI-725361, EBI-742038;
CC       Q9Y285; Q9H9E3: COG4; NbExp=3; IntAct=EBI-725361, EBI-368382;
CC       Q9Y285; Q9BQ95: ECSIT; NbExp=2; IntAct=EBI-725361, EBI-712452;
CC       Q9Y285; Q9NSD9: FARSB; NbExp=7; IntAct=EBI-725361, EBI-353803;
CC       Q9Y285; Q9BUL8: PDCD10; NbExp=3; IntAct=EBI-725361, EBI-740195;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q505J8}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9Y285-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9Y285-2; Sequence=VSP_056196;
CC   -!- DISEASE: Rajab interstitial lung disease with brain calcifications 2
CC       (RILDBC2) [MIM:619013]: An autosomal recessive disorder characterized
CC       by interstitial lung disease, growth delay, hypotonia, liver disease,
CC       and brain abnormalities including diffuse, symmetrical brain
CC       calcifications and periventricular cysts.
CC       {ECO:0000269|PubMed:31355908}. Note=The disease may be caused by
CC       variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC       Phe-tRNA synthetase alpha subunit type 2 subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB51175.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; U07424; AAB61694.1; -; mRNA.
DR   EMBL; AF042347; AAD02221.1; -; mRNA.
DR   EMBL; D84471; BAA95666.1; -; mRNA.
DR   EMBL; BT007198; AAP35862.1; -; mRNA.
DR   EMBL; AK304587; BAG65375.1; -; mRNA.
DR   EMBL; AD000092; AAB51175.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BC006495; AAH06495.1; -; mRNA.
DR   EMBL; BC043565; AAH43565.1; -; mRNA.
DR   CCDS; CCDS12287.1; -. [Q9Y285-1]
DR   PIR; T45074; T45074.
DR   RefSeq; NP_004452.1; NM_004461.2. [Q9Y285-1]
DR   PDB; 3L4G; X-ray; 3.30 A; A/C/E/G/I/K/M/O=1-508.
DR   PDBsum; 3L4G; -.
DR   AlphaFoldDB; Q9Y285; -.
DR   SMR; Q9Y285; -.
DR   BioGRID; 108487; 156.
DR   ComplexPortal; CPX-2208; Phenylalanyl-tRNA synthetase complex.
DR   DIP; DIP-53610N; -.
DR   IntAct; Q9Y285; 56.
DR   MINT; Q9Y285; -.
DR   STRING; 9606.ENSP00000320309; -.
DR   DrugBank; DB00120; Phenylalanine.
DR   GlyGen; Q9Y285; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9Y285; -.
DR   MetOSite; Q9Y285; -.
DR   PhosphoSitePlus; Q9Y285; -.
DR   SwissPalm; Q9Y285; -.
DR   BioMuta; FARSA; -.
DR   DMDM; 12643946; -.
DR   EPD; Q9Y285; -.
DR   jPOST; Q9Y285; -.
DR   MassIVE; Q9Y285; -.
DR   MaxQB; Q9Y285; -.
DR   PaxDb; 9606-ENSP00000320309; -.
DR   PeptideAtlas; Q9Y285; -.
DR   ProteomicsDB; 5881; -.
DR   ProteomicsDB; 85694; -. [Q9Y285-1]
DR   Pumba; Q9Y285; -.
DR   Antibodypedia; 1072; 158 antibodies from 25 providers.
DR   DNASU; 2193; -.
DR   Ensembl; ENST00000314606.9; ENSP00000320309.3; ENSG00000179115.11. [Q9Y285-1]
DR   Ensembl; ENST00000423140.6; ENSP00000396548.2; ENSG00000179115.11. [Q9Y285-2]
DR   GeneID; 2193; -.
DR   KEGG; hsa:2193; -.
DR   MANE-Select; ENST00000314606.9; ENSP00000320309.3; NM_004461.3; NP_004452.1.
DR   UCSC; uc002mvs.3; human. [Q9Y285-1]
DR   AGR; HGNC:3592; -.
DR   CTD; 2193; -.
DR   DisGeNET; 2193; -.
DR   GeneCards; FARSA; -.
DR   HGNC; HGNC:3592; FARSA.
DR   HPA; ENSG00000179115; Low tissue specificity.
DR   MalaCards; FARSA; -.
DR   MIM; 602918; gene.
DR   MIM; 619013; phenotype.
DR   neXtProt; NX_Q9Y285; -.
DR   OpenTargets; ENSG00000179115; -.
DR   PharmGKB; PA28005; -.
DR   VEuPathDB; HostDB:ENSG00000179115; -.
DR   eggNOG; KOG2784; Eukaryota.
DR   GeneTree; ENSGT00390000006387; -.
DR   HOGENOM; CLU_025086_2_2_1; -.
DR   InParanoid; Q9Y285; -.
DR   OMA; QIEGWVM; -.
DR   OrthoDB; 4619at2759; -.
DR   PhylomeDB; Q9Y285; -.
DR   TreeFam; TF300647; -.
DR   BRENDA; 6.1.1.20; 2681.
DR   PathwayCommons; Q9Y285; -.
DR   Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR   SignaLink; Q9Y285; -.
DR   SIGNOR; Q9Y285; -.
DR   BioGRID-ORCS; 2193; 818 hits in 1167 CRISPR screens.
DR   ChiTaRS; FARSA; human.
DR   GeneWiki; FARSA_(gene); -.
DR   GenomeRNAi; 2193; -.
DR   Pharos; Q9Y285; Tbio.
DR   PRO; PR:Q9Y285; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q9Y285; Protein.
DR   Bgee; ENSG00000179115; Expressed in prefrontal cortex and 194 other cell types or tissues.
DR   ExpressionAtlas; Q9Y285; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0009328; C:phenylalanine-tRNA ligase complex; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR   GO; GO:0004826; F:phenylalanine-tRNA ligase activity; IDA:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR   GO; GO:0006432; P:phenylalanyl-tRNA aminoacylation; IDA:UniProtKB.
DR   GO; GO:0051290; P:protein heterotetramerization; IDA:UniProtKB.
DR   CDD; cd00496; PheRS_alpha_core; 1.
DR   Gene3D; 1.10.10.2320; -; 1.
DR   Gene3D; 1.10.10.2330; -; 1.
DR   Gene3D; 3.30.1370.240; -; 1.
DR   InterPro; IPR006195; aa-tRNA-synth_II.
DR   InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR   InterPro; IPR004529; Phe-tRNA-synth_IIc_asu.
DR   InterPro; IPR002319; Phenylalanyl-tRNA_Synthase.
DR   InterPro; IPR040724; PheRS_DBD1.
DR   InterPro; IPR040586; PheRS_DBD2.
DR   InterPro; IPR040725; PheRS_DBD3.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   NCBIfam; TIGR00468; pheS; 1.
DR   PANTHER; PTHR11538:SF40; PHENYLALANINE--TRNA LIGASE ALPHA SUBUNIT; 1.
DR   PANTHER; PTHR11538; PHENYLALANYL-TRNA SYNTHETASE; 1.
DR   Pfam; PF18552; PheRS_DBD1; 1.
DR   Pfam; PF18554; PheRS_DBD2; 1.
DR   Pfam; PF18553; PheRS_DBD3; 1.
DR   Pfam; PF01409; tRNA-synt_2d; 1.
DR   SUPFAM; SSF55681; Class II aaRS and biotin synthetases; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
DR   Genevisible; Q9Y285; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase;
KW   ATP-binding; Cytoplasm; Direct protein sequencing; Disease variant; Ligase;
KW   Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW   Protein biosynthesis; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:12665801, ECO:0000269|Ref.9,
FT                   ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT                   ECO:0007744|PubMed:22814378, ECO:0007744|PubMed:25944712"
FT   CHAIN           2..508
FT                   /note="Phenylalanine--tRNA ligase alpha subunit"
FT                   /id="PRO_0000126824"
FT   BINDING         329
FT                   /ligand="L-phenylalanine"
FT                   /ligand_id="ChEBI:CHEBI:58095"
FT                   /evidence="ECO:0000269|PubMed:20223217,
FT                   ECO:0007744|PDB:3L4G"
FT   BINDING         372..374
FT                   /ligand="L-phenylalanine"
FT                   /ligand_id="ChEBI:CHEBI:58095"
FT                   /evidence="ECO:0000269|PubMed:20223217,
FT                   ECO:0007744|PDB:3L4G"
FT   BINDING         412
FT                   /ligand="L-phenylalanine"
FT                   /ligand_id="ChEBI:CHEBI:58095"
FT                   /evidence="ECO:0000269|PubMed:20223217,
FT                   ECO:0007744|PDB:3L4G"
FT   BINDING         414
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="shared with beta subunit"
FT                   /evidence="ECO:0000250|UniProtKB:A5K9S0"
FT   BINDING         438
FT                   /ligand="L-phenylalanine"
FT                   /ligand_id="ChEBI:CHEBI:58095"
FT                   /evidence="ECO:0000269|PubMed:20223217,
FT                   ECO:0007744|PDB:3L4G"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:19413330,
FT                   ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378,
FT                   ECO:0007744|PubMed:25944712"
FT   MOD_RES         190
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         193
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976"
FT   MOD_RES         301
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8C0C7"
FT   MOD_RES         311
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   VAR_SEQ         169..199
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_056196"
FT   VARIANT         256
FT                   /note="F -> L (in RILDBC2; uncertain significance;
FT                   dbSNP:rs941586004)"
FT                   /evidence="ECO:0000269|PubMed:31355908"
FT                   /id="VAR_084994"
FT   VARIANT         341
FT                   /note="Q -> R (in dbSNP:rs35087277)"
FT                   /id="VAR_052641"
FT   VARIANT         410
FT                   /note="N -> K (in RILDBC2; uncertain significance;
FT                   dbSNP:rs1971301248)"
FT                   /evidence="ECO:0000269|PubMed:31355908"
FT                   /id="VAR_084995"
FT   CONFLICT        179
FT                   /note="S -> G (in Ref. 3; BAA95666)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        376
FT                   /note="V -> L (in Ref. 3; BAA95666)"
FT                   /evidence="ECO:0000305"
FT   HELIX           4..16
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          17..19
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           25..28
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   TURN            29..31
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           37..41
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           43..46
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          53..61
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           65..73
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           76..83
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           91..94
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           98..108
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   TURN            109..111
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          112..114
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          119..121
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          126..128
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           135..143
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   TURN            144..149
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           153..161
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          167..175
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   TURN            194..198
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   TURN            201..204
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          212..214
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           226..240
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          251..254
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           255..258
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           260..262
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          266..268
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   TURN            273..275
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          278..280
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           290..301
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           316..319
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          321..324
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           329..340
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          342..344
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          348..357
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          364..366
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          368..381
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           384..396
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   TURN            397..399
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          404..407
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          414..421
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          430..436
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           440..443
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           444..446
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   STRAND          452..461
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           462..465
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   TURN            466..470
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           474..476
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   HELIX           484..489
FT                   /evidence="ECO:0007829|PDB:3L4G"
FT   TURN            497..499
FT                   /evidence="ECO:0007829|PDB:3L4G"
SQ   SEQUENCE   508 AA;  57564 MW;  99BC12E1F3C5FCFD CRC64;
     MADGQVAELL LRRLEASDGG LDSAELAAEL GMEHQAVVGA VKSLQALGEV IEAELRSTKH
     WELTAEGEEI AREGSHEARV FRSIPPEGLA QSELMRLPSG KVGFSKAMSN KWIRVDKSAA
     DGPRVFRVVD SMEDEVQRRL QLVRGGQAEK LGEKERSELR KRKLLAEVTL KTYWVSKGSA
     FSTSISKQET ELSPEMISSG SWRDRPFKPY NFLAHGVLPD SGHLHPLLKV RSQFRQIFLE
     MGFTEMPTDN FIESSFWNFD ALFQPQQHPA RDQHDTFFLR DPAEALQLPM DYVQRVKRTH
     SQGGYGSQGY KYNWKLDEAR KNLLRTHTTS ASARALYRLA QKKPFTPVKY FSIDRVFRNE
     TLDATHLAEF HQIEGVVADH GLTLGHLMGV LREFFTKLGI TQLRFKPAYN PYTEPSMEVF
     SYHQGLKKWV EVGNSGVFRP EMLLPMGLPE NVSVIAWGLS LERPTMIKYG INNIRELVGH
     KVNLQMVYDS PLCRLDAEPR PPPTQEAA
//